
Tomer Avidor-Reiss- Professor
- Professor at University of Toledo
Tomer Avidor-Reiss
- Professor
- Professor at University of Toledo
About
113
Publications
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Introduction
We study centrioles, centrosomes, and cilia in reproductive biology.
A video about our research is available here: http://sciencemission.com/index.php?page=tomer
Current institution
Additional affiliations
January 2013 - present
July 2005 - July 2012
Publications
Publications (113)
Centrosome reduction is the decrease in centrosomal components during spermatid differentiation (spermiogenesis) [1, 2]. It is one of several dramatic subcellular reorganizations that lead to spermatozoa formation common to a wide range of animals [3]. However, the mechanism underlying centrosome reduction is unknown and its functions are unclear....
Centrosomes are composed of two centrioles surrounded by pericentriolar material (PCM). However, the sperm and the oocyte modify or lose their centrosomes. Consequently, how the zygote establishes its first centrosome, and in particular, the origin of the second zygotic centriole, is uncertain. Drosophila melanogaster spermatids contain a single ce...
Most animals have two centrioles in spermatids (the distal and proximal centrioles), but insect spermatids seem to contain only one centriole (Fuller 1993), which functionally resembles the distal centriole. Using fluorescent centriolar markers, we identified a structure near the fly distal centriole that is reminiscent of a proximal centriole (i.e...
Spermatozoa reach the fallopian tube during ovulation by traveling through the female reproductive tract mucus. This non‐Newtonian viscoelastic medium facilitates spermatozoon movement to accomplish fertilization or, in some cases, blocks spermatozoon movement, leading to infertility. While rheological properties are known to affect spermatozoon mo...
Purpose
Spermatozoa centriolar defects can result in abnormal zygote functions. Recently, a method to quantify spermatozoa centriolar defects was developed named Fluorescence-Based Ratiometric Analysis of Sperm Centrioles (FRAC). However, whether spermatozoa centriolar defects identified by FRAC can result in abnormal zygote functions was not teste...
The centrosome is a conserved characteristic of eukaryotic and human cells but is highly specialized in reproductive cells. The spermatozoan centrosome includes a slightly modified proximal centriole, an atypical distal centriole, and specialized pericentriolar material, including striated columns and capitellum. We investigated the localization of...
Purpose:
This study investigated 1) the frequency of quotation errors in multi-authored medical manuscripts in andrology, 2) analyzed common types of quotation errors and the methods used to rectify them, and 3) evaluated their impact on manuscript accuracy, credibility, and research conclusions.
Materials and methods:
Twelve manuscripts written...
There is a well-established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associa...
Family with sequence similarity 161 (Fam161) is an ancient family of microtubule-binding proteins located at the centriole and cilium transition zone (TZ) lumen that exhibit rapid evolution in mice. However, their adaptive role is unclear. Here, we used flies to gain insight into their cell type-specific adaptations. Fam161 is the sole orthologue o...
There is a well–established link between abnormal sperm chromatin states and poor motility, however, how these two processes are interdependent is unknown. Here, we identified a possible mechanistic insight by showing that Protamine 2, a nuclear DNA packaging protein in sperm, directly interacts with cytoskeletal protein Septin 12, which is associa...
The article by Nils Kalbfuss & Pierre Gönczy [1] is devoted to one of the least
explored issues of centrosome function in the cell—the mechanisms of centriole
elimination. This commentary discusses previously described examples of such
elimination and their significance for individual cells and animals as a whole in
the context of reproduction. We...
Centrioles form centrosomes that organize microtubules, assist in cell structure, and nucleate cilia that provide motility and sensation. Within the sperm, the centrosome consists of two centrioles (proximal and distal centriole) and a pericentriolar material known as the striated column and capitulum. The distal centriole nucleates the flagellum....
Centrioles are subcellular organelles found at the cilia base with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles are found at the flagellum base and are essential for embryo development in basal animals. Yet, sperm centrioles have evolved diverse forms, sometimes acting like a transmission system, as...
The mechanisms underlying male infertility are poorly understood. Most mammalian spermatozoa have two centrioles: the typical barrel-shaped proximal centriole (PC) and the atypical fan-like distal centriole (DC) connected to the axoneme (Ax). These structures are essential for fertility. However, the relationship between centriole quality and subfe...
A prominent technical barrier when imaging swimming sperm is capturing a singular sperm cell’s head and tail position simultaneously at a high resolution to understand their relationship in different stages of the sperm tail beating cycle. This is due to the sperm’s high beating frequency, rotational movement, and the large difference in diameter b...
Purpose:
Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recom...
Centrosomes play an important role in the microtubule organization of a cell. The sperm's specialized centrosome consists of the canonical barrel-shaped proximal centriole, the funnel-shaped distal centriole, and the pericentriolar material known as striated columns (or segmented columns). Here, we examined the localization of the centriole protein...
The prevailing assumption has been that the human spermatozoon provides only one centriole to the zygote: the proximal centriole, with a canonical, cylinder-like shape. This overly simplistic view has come under challenge since discovering that the human spermatozoon provides a second, atypical centriole to the zygote. The study of human zygotes is...
Purpose:
Sperm DNA fragmentation (SDF) is a functional sperm abnormality that can impact reproductive potential, for which four assays have been described in the recently published sixth edition of the WHO laboratory manual for the examination and processing of human semen. The purpose of this study was to examine the global practices related to t...
The mechanisms underlying male infertility are poorly understood. Most mammalian spermatozoa have two centrioles: the typical barrel-shaped proximal centriole (PC) and the atypical fan-like distal centriole (DC) connected to the axoneme (Ax). These structures are essential for fertility. However, the relationship between centriole quality and subfe...
Artificial intelligence (AI) in medicine has gained a lot of momentum in the last decades and has been applied to various fields of medicine. Advances in computer science, medical informatics, robotics, and the need for personalized medicine have facilitated the role of AI in modern healthcare. Similarly, as in other fields, AI applications, such a...
Centrioles are microtubule-based, barrel-shaped, subcellular organelles with evolutionarily conserved composition, structure, and function. Yet, in sperm cells, centrioles are remodeled, gaining species-specific composition and structure. The sperm centrioles of Drosophila melanogaster undergo dramatic remodeling, during which most known centriolar...
Centrosome formation during early development in mice and rats occurs due to the appearance of centrioles de novo. In contrast, in humans and other non-rodent mammals, centrioles are thought to be derived from spermatozoa. Ultrastructural study of zygotes and early embryos of cattle at full series of ultrathin sections show that the proximal centri...
Centrioles are subcellular organelles with an evolutionarily conserved structure and a shock absorber-like function. In sperm, centrioles are found at the flagellum base and are essential for embryo development in basal animals. Yet, sperm centrioles have evolved diverse forms, sometimes acting like a transmission system, as in cattle, and sometime...
Infertility affects nearly 186 million people worldwide and the male partner is the cause in about half of the cases. Meta-regression
data indicate an unexplained decline in sperm concentration and total sperm count over the last four decades, with
an increasing prevalence of male infertility. This suggests an urgent need to implement further basic...
Sperm cells have intrigued biologists since they were first observed nearly 350 years ago by Antonie van Leeuwenhoek and Johan Ham [...]
The centrosome consists of two centrioles surrounded by pericentriolar material [...]
Centrosome formation during early development in mice and rats occurs due to the appearance of centrioles de novo. In contrast, in humans and other non-rodent mammals, centrioles are thought to be derived from spermatozoa. Ultrastructural study of zygotes and early embryos of cattle at full series of ultrathin sections showed that the proximal cent...
Sperm cells are transcriptionally and translationally silent. Therefore, they may use one of the remaining mechanisms to respond to stimuli in their environment, the post-translational modification of their proteins. Here we examined three post-translational modifications, acetylation, glutamylation, and glycylation of the protein tubulin in human...
Unexplained infertility affects about one-third of infertile couples and is defined as the failure to identify the cause of infertility despite extensive evaluation of the male and female partners. Therefore, there is a need for a multiparametric approach to study sperm function. Recently, we developed a Fluorescence-Based Ratiometric Analysis of S...
Centrioles are subcellular organelles essential for normal cell function and development; they form the cell’s centrosome (a major cytoplasmic microtubule organization center) and cilium (a sensory and motile hair-like cellular extension). Centrioles with evolutionarily conserved characteristics are found in most animal cell types but are absent in...
The sperm competition theory, as proposed by Geoff Parker, predicts that sperm evolve through a cascade of changes. As an example, internal fertilization is followed by sperm morphology diversification. However, little is known about the evolution of internal sperm structures. The centriole has an ancient and evolutionarily conserved canonical stru...
The embryo of humans and other mammals requires the presence of two subcellular structures, named centrioles. The centrioles act as nucleation points for two massive structures that help build the skeleton of the cell, the centrosome, and the cilium. Centrosomes nucleate and anchor star-shaped arrays of microtubules known as asters that assist in c...
Reproductive success depends on efficient sperm movement driven by axonemal dynein-mediated microtubule sliding. Models predict sliding at the base of the tail – the centriole – but such sliding has never been observed. Centrioles are ancient organelles with a conserved architecture; their rigidity is thought to restrict microtubule sliding. Here,...
Male-factor infertility affects millions of couples worldwide. Due to a lack of alternatives, many couples ultimately resort to In Vitro fertilization (IVF) with Intracytoplasmic Sperm Injection (ICSI). This treatment puts most of the infertility burden on the female partner and requires an invasive surgical procedure. The availability of IVF/ICSI...
A large proportion of infertility and miscarriage causes are unknown. One potential cause is a defective sperm centriole, a subcellular structure essential for sperm motility and embryonic development. Yet, the extent to which centriolar maladies contribute to male infertility is unknown due to the lack of a convenient way to assess centriole quali...
Reproductive success depends on efficient sperm movement driven by dynein-mediated microtubule sliding in the axoneme 1-3. Models predict sliding at the base of the tail – the centriole – but such sliding has never been observed 4,5. Centrioles are evolutionarily-ancient organelles with a conserved architecture 6-8, and their rigidity is thought to...
Reproductive success depends on efficient sperm movement driven by dynein-mediated microtubule sliding in the axoneme ¹⁻³ . Models predict sliding at the base of the tail – the centriole – but such sliding has never been observed 4,5 . Centrioles are evolutionarily-ancient organelles with a conserved architecture ⁶⁻⁸ , and their rigidity is thought...
Semen analysis is the cornerstone of evaluating male infertility, but it is imperfect and insufficient to diagnose male infertility. As a result, about 20% of infertile males have undetermined infertility, a term encompassing male infertility with an unknown underlying cause. Undetermined male infertility includes two categories: (i) idiopathic mal...
Reproductive success depends on efficient sperm movement driven by dynein-mediated microtubule sliding in the axoneme 1-3. Models predict sliding at the base of the tail – the centriole – but such sliding has never been observed 4,5. Centrioles are evolutionarily-ancient organelles with a conserved architecture 6-8, and their rigidity is thought to...
Clinically, infertility is defined as the inability to conceive after a certain period. In contrast, sterility is defined as the inability to produce a biological child; however, this is not a practical definition that can be applied in a clinical setting to a patient's diagnosis. Unlike infertility, sterility is rarely discussed in biomedical and...
The centrosome, which consists of two centrioles surrounded by pericentriolar material, is a unique structure that has retained its main features in organisms of various taxonomic groups from unicellular algae to mammals over one billion years of evolution. In addition to the most noticeable function of organizing the microtubule system in mitosis...
The centrosome, which consists of two centrioles surrounded by pericentriolar material, is a unique structure that has retained its main features in organisms of various taxonomic groups from unicellular algae to mammals over one billion years of evolution. In addition to the most noticeable function of organizing the microtubule system in mitosis...
Centrioles are eukaryotic subcellular structures that produce and regulate massive subcellular cytoskeleton superstructures. They form centrosomes and cilia, regulate new centriole formation, secure cilia to the cell, and regulate cilia function. These basic centriolar functions are executed in sperm cells during their amplification from spermatogo...
Infertility is a devastating experience for both partners as they try to conceive. Historically, when a couple could not conceive, the woman has carried the stigma of infertility; however, men and women are just as likely to contribute to the couple’s infertility. With the development of assisted reproductive technology (ART), the treatment burden...
Each human spermatozoon contains two remodeled centrioles that it contributes to the zygote. There, the centrioles reconstitute a centrosome that assembles the sperm aster and participate in pronuclei migration and cleavage. Thus, centriole abnormalities may be a cause of male factor infertility and failure to carry pregnancy to term. However, the...
Insects and mammals have atypical centrioles in their sperm. However, it is unclear how these atypical centrioles form. Drosophila melanogaster sperm has one typical centriole called the giant centriole (GC) and one atypical centriole called the proximal centriole-like structure (PCL). During early sperm development, centriole duplication factors s...
Centrioles are subcellular organelles that were present in the last eukaryotic common ancestor, where the centriole’s ancestral role was to form cilia. Centrioles have maintained a remarkably conserved structure in eukaryotes that have cilia, while groups that lack cilia have lost their centrioles, highlighting the structure–function relationship t...
Cells that divide during embryo development require precisely two centrioles during interphase and four centrioles during mitosis. This precise number is maintained by allowing each centriole to nucleate only one centriole per cell cycle (i.e. centriole duplication). Yet, how the first cell of the embryo, the zygote, obtains two centrioles has rema...
In the original version of this Article, the affiliation details for Jadranka Loncarek and Vito Mennella were incorrectly given as 'Cell Biology Program, The Hospital for Sick Children, Department of Biochemistry, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada' and 'Laboratory of Protein Dynamics and Signaling, Center fo...
Centrioles are ancient subcellular protein-based organelles that maintain a conserved number and structure across many groups of eukaryotes. Centriole number (two per cells) is tightly regulated; each pre-existing centriole nucleates only one centriole as the cell prepares for division. The structure of centrioles is barrel-shaped, with a nine-fold...
The inheritance of the centrosome during human fertilization remains mysterious. Here we show that the sperm centrosome contains, in addition to the known typical barrel-shaped centriole (the proximal centriole, PC), a surrounding matrix (pericentriolar material, PCM), and an atypical centriole (distal centriole, DC) composed of splayed microtubule...
Typical centrioles are made of microtubules organized in ninefold symmetry. Most animal somatic cells have two centrioles for normal cell division and function. These centrioles originate from the zygote, but because the oocyte does not provide any centrioles, it is surprising that the zygotes of many animals are thought to inherit only one centrio...
The cilium is an elongated and continuous structure that spans two major subcellular domains. The cytoplasmic domain contains a short centriole, which serves to nucleate the main projection of the cilium. This projection, known as the axoneme, remains separated from the cytoplasm by a specialized gatekeeping complex within a ciliary subdomain calle...
The first cell of an animal (zygote) requires centrosomes that are assembled from paternally inherited centrioles and maternally inherited pericentriolar material (PCM) [1]. In some animals, sperm centrioles with typical ultrastructure are the origin of the first centrosomes in the zygote [2–4]. In other animals, however, sperm centrioles lose thei...
Most motile and all non-motile (also known as primary) eukaryotic cilia possess microtubule-based axonemes that are assembled at the cell surface to form hair-like or more elaborate compartments endowed with motility and/or signaling functions. Such compartmentalized ciliogenesis depends on the core intraflagellar transport (IFT) machinery and the...
The primary cilium compartmentalizes a tiny fraction of the cell surface and volume, yet many proteins are highly enriched in this area and so efficient mechanisms are necessary to concentrate them in the ciliary compartment. Here we review mechanisms that are thought to deliver protein cargo to the base of cilia and are likely to interact with cil...
Significance
In centrosomes, pericentriolar material (PCM) serves as the principle site for microtubule nucleation and anchoring. In Drosophila , the centrosomal protein spindle assembly defective-4 (Sas-4) scaffolds cytoplasmic PCM protein complexes via its N terminus and tethers them to centrioles via an unknown mechanism. By determining the crys...
Centrosomes and cilia are conserved microtubule-based organelles whose structure and function depend on cell cycle stages. In dividing cells, centrosomes organize mitotic spindle poles, while in differentiating cells, centrosomes template ciliogenesis. Classically, this functional dichotomy has been attributed to regulation by cell cycle-dependent...
Centrosomes are conserved microtubule-based organelles whose structure and function change dramatically throughout the cell cycle and cell differentiation. Centrosomes are essential to determine the cell division axis during mitosis and to nucleate cilia during interphase. The identity of the proteins that mediate these dynamic changes remains only...
Centrioles are the key foundation of centrosomes and cilia, yet a molecular understanding of how they form has only recently begun to emerge. Building a fully functional centriole that can form a centrosome and cilium requires two cell cycles. Centriole building starts with procentriole nucleation, a process that is coordinated by the conserved pro...
Centrosomes are conserved microtubule-based organelles that are essential for animal development. In this chapter, we highlight key centrosomal proteins and describe the centrosome in the context of several developmental processes in Drosophila melanogaster. These processes include fertilization, during which the centrosome mediates the fusion of m...
Regulated centrosome biogenesis is required for accurate cell division and for maintaining genome integrity. Centrosomes consist of a centriole pair surrounded by a protein network known as pericentriolar material (PCM). PCM assembly is a tightly regulated, critical step that determines the size and capability of centrosomes. Here, we report a role...
Centrosomes are conserved organelles that are essential for accurate cell division and cilium formation. A centrosome consists of a pair of centrioles surrounded by a protein network of pericentriolar material (PCM) that is essential for the centrosome's function. In this study, we show that Sas-4 provides a scaffold for cytoplasmic complexes (name...
Centrioles are conserved microtubule-based organelles with 9-fold symmetry that are essential for cilia and mitotic spindle formation. A conserved structure at the onset of centriole assembly is a "cartwheel" with 9-fold radial symmetry and a central tubule in its core. It remains unclear how the cartwheel is formed. The conserved centriole protein...
We have investigated the expression and function of the Sox15 transcription factor during the development of the external mechanosensory organs of Drosophila. We find that Sox15 is expressed specifically in the socket cell, and have identified the transcriptional cis-regulatory module that controls this activity. We show that Suppressor of Hairless...
The centriole is the core structure of centrosome and cilium. Failure to restrict centriole duplication to once per cell cycle has serious consequences and is commonly observed in cancer. Despite its medical importance, the mechanism of centriole formation is poorly understood. Asl was previously reported to be a centrosomal protein essential for c...
It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed
AC superactivation (or supersensitization). More recently, we showed that acute Gi/o-coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chr...
We previously reported that acute agonist activation of G(i/o)-coupled receptors inhibits adenylate cyclase (AC) type VIII activity, whereas agonist withdrawal following chronic activation of these receptors induces AC-VIII superactivation. Three splice variants of AC-VIII have been identified, which are called AC-VIII-A, -B and -C (with AC-VIII-B...
It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o- coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas ch...
The evolution of the ancestral eukaryotic flagellum is an example of a cellular organelle that became dispensable in some modern eukaryotes while remaining an essential motile and sensory apparatus in others. To help define the repertoire of specialized proteins needed for the formation and function of cilia, we used comparative genomics to analyze...
The evolution of the ancestral eukaryotic flagellum is an example of a cellular organelle that became dispensable in some modern eukaryotes while remaining an essential motile and sensory apparatus in others. To help define the repertoire of specialized proteins needed for the formation and function of cilia, we used comparative genomics to analyze...
Although it is well-established that G protein-coupled receptor signaling systems can network with those of tyrosine kinase receptors by several mechanisms, the point(s) of convergence of the two pathways remains largely undelineated, particularly for opioids. Here we demonstrate that opioid agonists modulate the activity of the extracellular signa...
Many types of cells exhibit increased adenylyl cyclase (AC) activity after chronic agonist treatment of G(i/o)-coupled receptors. This phenomenon, defined as AC superactivation or sensitization, has mostly been studied for the opioid receptors and is implicated in opiate addiction. Here we show that this phenomenon is also observed on chronic activ...
Prolonged G(i/o) protein-coupled receptor activation has been shown to lead to receptor internalization and receptor desensitization. In addition, it is well established that although acute activation of these receptors leads to inhibition of adenylyl cyclase (AC), long-term activation results in increased AC activity (especially evident on removal...
While acute activation of G(i/o)-coupled receptors leads to inhibition of adenylyl cyclase, chronic activation of such receptors produces an increase in cyclic AMP accumulation, particularly evident upon withdrawal of the inhibitory agonist. This phenomenon has been referred to as adenylyl cyclase superactivation and is believed to play an importan...
1.The D2-type dopamine receptors are thought to inhibit adenylyl cyclase (AC), via coupling to pertussis toxin (PTX)-sensitive G proteins of the Gi family. We examined whether and to what extent the various D2 receptors (D2S, D2L, D3S, D3L, and D4) couple to the PTX-insensitive G protein Gz, to produce inhibition of AC activity.
2.COS-7 cells were...
Two cannabinoid receptors belonging to the superfamily of G protein-coupled membrane receptors have been identified and cloned: the neuronal cannabinoid receptor (CB1) and the peripheral cannabinoid receptor (CB2). They have been shown to couple directly to the G(i/o) subclass of G proteins and to mediate inhibition of adenylyl cyclase upon binding...
An intriguing development in the G-protein signaling field has been the finding that not only the Galpha subunit, but also Gbetagamma subunits, affect a number of downstream target molecules. One of the downstream targets of Gbetagamma is adenylyl cyclase, and it has been demonstrated that a number of isoforms of adenylyl cyclase can be either inhi...
Adenylyl cyclase superactivation, a phenomenon by which chronic activation of inhibitory Gi/o-coupled receptors leads to an increase in cAMP accumulation, is believed to play an important role as a compensatory response of the cAMP signaling system in the cell. However, to date, the mechanism by which adenylyl cyclase activity is regulated by chron...
An intriguing development in the G- protein signaling field has been the finding that not only the Ga subunit, but also Gbg subunits, affect a number of downstream target molecules. One of the downstream targets of Gbg is adenylyl cyclase, and it has been demonstrated that a number of isoforms of adenylyl cyclase can be either inhibited or stimulat...
Although it is well-established that G protein-coupled receptor signaling systems can network with those of tyrosine kinase receptors by several mechanisms, the point(s) of convergence of the two pathways remains largely undelineated, particularly for opioids. Here we demonstrate that opioid agonists modulate the activity of the extracellular signa...
The accepted dogma concerning the regulation of adenylyl cyclase (AC) activity by G beta gamma dimers states that the various isoforms of AC respond differently to the presence of free G beta gamma. It has been demonstrated that AC I activity is inhibited and AC II activity is stimulated by G beta gamma subunits. This result does not address the po...
The accepted dogma concerning the regulation of adenylyl cyclase (AC) activity by Gβγ dimers states that the various isoforms of AC respond differently to the presence of free Gβγ. It has been demonstrated that AC I activity is inhibited and AC II activity is stimulated by Gβγ subunits. This result does not address the possible differences in modul...
The accepted dogma concerning the regulation of adenylyl cyclase (AC) activity by Gβγ dimers states that the various isoforms of AC respond differently to the presence of free Gβγ. It has been demonstrated that AC I activity is inhibited and AC II activity is stimulated by Gβγ subunits. This result does not address the possible differences in modul...